Metabolic changes commonly occur in HIV therapy. The purpose of this study is to assess the impact on insulin sensitivity from the administration of tenofovir disoproxil fumarate 300 mg compared with placebo in non-HIV-1 infected healthy adult males. Additionally, endothelial function, adipocytokines and lipids will be monitored.

To assess the impact on insulin sensitivity (determined by peripheral glucose uptake suing a euglycaemic clamp) of the administration of tenofovir DF compared with placebo for two weeks in HIV-1 seronegative healthy male volunteers.

Secondary Outcome Measures:

To assess endothelial function by monitoring changes in Selectin P/E and PAI-1 assays.

To monitor adipocytokines by assessing adiponectin and leptin levels.

To monitor lipids by assessing large and small lipoprotein sub-fractions of HDL and LDL cholesterol, triglycerides, and non esterified fatty acid concentrations.

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the first 14 days of the study.

Tenofovir DF placebo tablet QD for the last 14 days of the study.

Drug: Tenofovir Disoproxil Fumarate

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil)

Drug: Tenofovir DF placebo

Tenofovir DF placebo tablet QD

Active Comparator: Group 2

Tenofovir DF placebo tablet QD for the first 14 days of the study.

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the last 14 days of the study.

Drug: Tenofovir Disoproxil Fumarate

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil)

Drug: Tenofovir DF placebo

Tenofovir DF placebo tablet QD

Detailed Description:

Double-blind, randomized, placebo-controlled study using a two-sequence two-period crossover structure. Sixteen HIV-1-negative males will be randomized 1:1 to one of two treatment arms.

Group 1:

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the first 14 days of the study.

Tenofovir DF placebo tablet QD for the last 14 days of the study.

Group 2:

Tenofovir DF placebo tablet QD for the first 14 days of the study.

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the last 14 days of the study.

Physical examinations and laboratory analyses are conducted at screening, baseline, Day 14, and Day 28. A euglycaemic clamp protocol and an ECG are performed at the baseline, Day 14 and Day 28 visits.

The primary efficacy endpoint of this study is insulin-mediated glucose disposal during a hyperinsulinaemic euglycaemic clamp study. Endothelial function will be monitored by Selectin P/E and PAI-1 levels; adipocytokine levels will be monitored by measuring adiponectin and leptin levels; and lipid subfractions, including cholesterol (large and small subfractions of HDL and LDL) triglycerides and non-esterified fatty acids will be measured. Safety will be evaluated by adverse event and clinical laboratory test reporting.

Eligibility

Ages Eligible for Study:

18 Years to 55 Years

Genders Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Subjects must have documented negative HIV serology by ELISA and P24 antigen. This will be done at the screening visit.

Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00648817